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EC number: 249-854-8 | CAS number: 29797-40-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Short description of key information:
In vitro:
Two Ames tests are available: In one test 5 strains were tested, in the
other 4 strains were used.
Additionally, the test item was tested in an HPRT assay according OECD
Guideline study 476. Under the experimental conditions reported the test
item did not induce gene mutations at the HPRT locus in V79 cells and
therefore was considered to be non-mutagenic in this HPRT assay (Hall/
Harlan/ Lanxess, 2010).
In vivo:
In a micronucleus test according to OECD guideline 474 no indications of
a clastogenic effect of the test substance dichlorotoluene (mixture of
isomers) were found after a single intraperitoneal treatment with 1500
mg/kg (Herbold/ Bayer AG, 1993).
Overall, it can be concluded that the compound is not genotoxic in vitro
or in vivo.
Endpoint Conclusion: No adverse effect observed (negative).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- The test item 'Dichlortoluol Gemisch' was initially investigated for point mutagenic effects in the plate incorporation test. The test item, dissolved in DMSO, was administered in doses of up to and including 5000 µg per plate without and with S9 mix on the five Salmonella typhimurium LT2 mutant strains TA1535, TA100, TA1537, TA98 and TA102, according to the OECD guideline 471.
The test item was investigated in an independent repeat using the preincubation modification in doses of up to and including 500 µg per plate without and with S9 mix. Other experimental conditions remained unchanged. - GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: TA1535, TA100, TA1537, TA98 and TA102
- Additional strain / cell type characteristics:
- other: All S. typhimurium strains were checked for of rfa-mutation ("deep rough"), for their resistance to ampicillin to establish the presence ofthe R-factor/pKM101-plasmid and for their resistance to tetracycline to establish the presence ofthe pAQ1-plasmid
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- plate incorporation test: up to and including 5000 µg per plate without and with S9 mix
preincubation method: up to and including 500 µg per plate without and with S9 mix - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- sodium azide
- cumene hydroperoxide
- mitomycin C
- other: 4-Nitro-1,2-phenylene diamine, 2-aminoanthracene
- Species / strain:
- S. typhimurium, other: TA1535, TA100, TA1537, TA98 and TA102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: Doses up to and including 160 µg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: other: TA1535, TA100, TA1537, TA98 and TA102
- Conclusions:
- Interpretation of results: negative
- Executive summary:
The test item 'Dichlortoluol Gemisch' was initially investigated for point mutagenic effects in the plate incorporation test. The test item, dissolved in DMSO, was administered in doses of up to and including 5000 µg per plate without and with S9 mix on the five Salmonella typhimurium LT2 mutant strains TA1535, TA100, TA1537, TA98 and TA102, according to the OECD guideline 471. Doses up to and including 160 µg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect. This range could be used strain-specific up to 5000 µg per plate for assessment purposes.
The test item was investigated in an independent repeat using the preincubation modification in doses of up to and including 500 µg per plate without and with S9 mix. Other experimental conditions remained unchanged. Doses up to and including 16 µg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect. This range could be used strain-specific up to 500 µg per plate for assessment purposes.
Evidence of mutagenic activity of the test item was not seen. No biologically relevant increase in the mutant count, in comparison to the solvent controls, was observed in any of the strains tested, without and with S9 mix, in the plate incorporation as well in the preincubation modification, under the experimental conditions applied.
Therefore, the test item was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: OECD Guideline study , only 4 strains tested
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- Only 4 strains tested.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Ames Test
- Species / strain / cell type:
- other: S. typhimurium TA 98, 100, 1535, 1537
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- up to 5000 µg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: Sodium azide for TA 1535, Nitrofurantoin for TA 100, 4-nitro-1,2-phenylene diamine for TA 1537 and TA 98, 2-aminoanthracene serves as a control for the activating effect of the S9 mix.
- Details on test system and experimental conditions:
- Ames test
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Conclusions:
- Interpretation of results: negative
- Executive summary:
The test substance was investigated using the Salmonella/microsome test for point mutagenic effects in doses up to 5000 µg per plate on four histidine-auxotrophic Salmonella typhimurium LT2 mutant strains (TA 1535, TA 100, TA 98, and TA 1537).
Doses up to and including 50 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no inhibition of growth was observed. At higher doses, the substance had a strong bacteriotoxic effect, but this range could nevertheless be used for assessment purposes.
The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.
Evidence of mutagenic activity of the test substance was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. Therefore, the test substance was considered to be non-mutagenic with and without S9 mix in the Salmonella/microsome test.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Regulation (EC) No. 440/2008 B.17: ”Mutagenicity – In vitro Mammalian Cell Gene Mutation Test“, dated May 30, 2008.
- GLP compliance:
- yes
- Type of assay:
- other: GENE MUTATION ASSAY IN CHINESE HAMSTER V79 CELLS IN VITRO
- Target gene:
- HPRT gen-lokus
- Species / strain / cell type:
- other: CHINESE HAMSTER V79 CELLS
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Experiment I (concentrations in µg/mL)
Exposure period: 4 hours, without S9 mix, 3.1, 6.3, 12.5, 25.0, 37.5, 50.0, 75.0;
Exposure period: 4 hours, with S9 mix, 12.5, 25.0, 50.0, 100.0, 150.0, 200.0, 300.0;
Experiment II (concentrations in µg/mL)
Exposure period: 24 hours, without S9 mix, 5.0, 10.0, 20.0*, 40.0, 60.0 ,80.0, 100.0*;
Exposure period: 4 hours**, with S9 mix, 50.0, 100.0, 150.0, 175.0, 200.0 250.0, 300.0;
Exposure period: 4 hours, with S9 mix, 9.4 18.8, 37.5, 75.0, 150.0, 200.0, 250.0
* was evaluated for mutagenicity only in one culture
** was repeated due to strong cytotoxicity - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: Without metabolic activation: EMS; ethylmethane sulfonate , With metabolic activation: DMBA; 7,12-dimethylbenz(a)anthracene
- Species / strain:
- other: CHINESE HAMSTER V79 CELLS
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results: negative
- Executive summary:
The study was performed to investigate the potential of Dichlortoluol-Gemisch to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activa-tion and a treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The highest concentration in the pre-experiment (1640.0 µg/mL) was equal to a molar concentration of about 10 mM, with respect to the purity of the test item (98.4 %). The dose range of the main experiments was limited by test item induced cytotoxicity.
No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments. Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.
In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, Dichlortoluol-Gemisch is considered to be non-mutagenic in this HPRT assay.
Referenceopen allclose all
Evidence of mutagenic activity ofthe test item was not seen. No biologically relevant increase in the mutant count, in comparison to the solvent controls, was observed in any of the strains tested, without and with S9 mix, in the plate incorporation as well in the preincubation modification, under the experimental conditions applied.
Summary of the Results With Dichlorotoluene (Isomer mixture) in the Salmonella/Microsome Test:
S9 mix | TA 1535 | TA 100 | TA 1537 | TA 98 |
without | negative | negative | negative | negative |
with | negative | negative | negative | negative |
The test item Dichlortoluol-Gemisch was assessed for its potential to induce gene muta-tions at the HPRT locus using V79 cells of the Chinese hamster. The study was performed in two independent experiments, using identical experimental conditions. In the first experiment the treatment period was 4 hours with and without meta-bolic activation. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation.
The maximum concentration of the test item applied in the pre-experiments equals a molar concentration of 10 mM, with respect to the purity of the test item (98.4 %). Due to strong test item induced cytotoxicity the concentrations applied in the main experiments were lower. In the main experiments no precipitation of the test item was observed up to the maximum concentration in all experiments. The maximum concentrations evaluated for mutagenicity were limited by strong cytotoxic effects. Except of the experimental part with S9 mix in experiment II the survival and/or the relative cell density were reduced to below 20 % in the highest evaluated dose group.
No relevant and reproducible increase in mutant colony numbers/106 cells was observed in the main experiments up to the maximum concentration. Predominantly the mutant fre-quencies remained well within the historical range of solvent controls. In experiment I in the absence of S9 mix and in experiment II in culture II several values (32.7 to 66.3 mutant colonies/106 cells) exceeded the respective solvent control data ranges. These values were either not reproducible in the parallel culture or were only slightly higher than the corresponding historical data range (experiment I, treatment with 6.3 µg/mL in the absence of S9 mix). The induction factor exceeded the threshold of three times the corresponding solvent control in the second culture of the experiment I without metabolic activation at 6.3 µg/mL and in the first culture of experiment II at 10.0 and 20.0 µg/mL (without S9 mix). This effect however, was judged to be based upon the rather low solvent controls of 9.7 and 7.6 mutant colonies/106 cells, respectively.
A linear regression analysis (least squares) was performed to assess a possible dose dependent increase of mutant frequencies using SYSTAT 11 statistics software. A significant dose dependent trend of the mutation frequency indicated by a probability value of <0.05 was solely detected in the second culture of the first experiment without metabolic activation. This trend however, was judged as irrelevant since it actually was reciprocal, going down versus increasing concentrations.
In both experiments of this study (with and without S9 mix) the range of the solvent con-trols was from 7.6 up to 39.0 mutants per 106 cells; the range of the groups treated with the test item was from 0.0 up to 66.3 mutants per 106 cells.
The mutagenicity frequencies of the solvent controls in experiment I, culture I and experi-ment II, culture II without metabolic activation (39.0 and 32.1 mutant colonies per 106 cells) slightly exceeded the historical range of solvent control (0.6 to 32.4 and 2.2 – 31.5 mutant colonies per 106 cells). However, this effect was judged as irrelevant since it is very minor and the corresponding solvent control in the parallel cultures remained well within the range of historical controls.
EMS (150 µg/mL) and DMBA (1.1 µg/mL) were used as positive controls and showed a distinct increase in induced mutant colonies.
In conclusion it can be stated that under the ex¬perimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, Dichlortoluol-Gemisch is considered to be non-mutagenic in this HPRT assay.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Short description of key information:
In vivo:
In a micronucleus test according to OECD guideline 474 no indications of
a clastogenic effect of the test substance dichlorotoluene (mixture of
isomers) were found after a single intraperitoneal treatment with 1500
mg/kg (Herbold/ Bayer AG, 1993).
Endpoint Conclusion: No adverse effect observed (negative).
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Route of administration:
- intraperitoneal
- Duration of treatment / exposure:
- single treatment
- Frequency of treatment:
- single treatment
- Post exposure period:
- Time of sacrifice:
negative control: 24 hrs,
test substance: 16, 24, 48 hrs,
positive control cyclophosphamide: 24 hrs - Remarks:
- Doses / Concentrations:
1500 mg/kg bw
Basis: - No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- not specified
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results (migrated information): negative
- Executive summary:
This micronucleus test was conducted to investigate the test substance dichlorotoluene (mixture of isomers) in male and female mice for a possible clastogenic effect on the chromosomes of bone marrow erythroblasts. The known clastogen and cytostatic agent, cyclophosphamide, served as control.
The treated animals received a single intraperitoneal administration of either the test substance or cyclophosphamide. The femoral marrow of groups treated with the test substance was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of the test substance and the positive control, cyclphosphamide, were 1500 and 20 mg/kg body weight, respectively.
The animals treated with the test substance showed symptoms of toxicity (apathy, stretching of body, roughed fur, staggering gait, spasm and difficulty in breathing) after administration. However, all animals survived untill the end of the test.
There was no altered ratio between polychromatic and normochromatic erythrocytes.
Cyclophosphamide, the positive control, had a clear clastogenic effect, as is shown by the biologically relevant increase in polychromatic erythrocytes with micronuclei. The ratio of polychromatic to normochromatic erythrocytes was not altered.
No indications of a clastogenic effect of the test substance dichlorotoluene (mixture of isomers) were found after a single intraperitoneal treatment with 1500 mg/kg.
Reference
Summary of results of Micronucleus test with Dichlorotoluene (mixture of isomers) (after acute intraperitoneal treatment with 1500 mg/kg body weight:
micronucleated cells per 1000 | ||||
experimental groups | number of evaluated polychromatic erythrocytes | number of normochromatic erythrocytes per 1000 polychromatic erythrocytes | normochromatic erythrocytes | polychromatic erythrocytes |
negative control | 10.000 | 1138 + 460 | 2.0 + 2.5 | 2.0 + 2.2 |
test substance 16 hrs | 10.000 | 977 + 232 | 1.9 + 1.3 | 1.7 + 1.5 |
test substance 24 hrs | 10.000 | 1149 + 243 | 1.9 + 1.2 | 2.0 + 1.8 |
test substance 48 hrs | 10.000 | 870 + 242 | 2.2 + 2.0 | 2.3 + 1.8 |
positive control CP 20 mg/kg | 10.000 | 728 + 227 | 1.6 + 1.4 | 19.1* + 10.4 |
*P< 0.01 in non-parametric Wilcoxon ranking test
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In vitro:
Ames Test by Nern, 2014: The test item 'Dichlortoluol Gemisch' was initially investigated for point mutagenic effects in the plate incorporation test. The test item, dissolved in DMSO, was administered in doses of up to and including 5000 µg per plate without and with S9 mix on the five Salmonella typhimurium LT2 mutant strains TA1535, TA100, TA1537, TA98 and TA102, according to the OECD guideline 471. Doses up to and including 160 µg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect. This range could be used strain-specific up to 5000 µg per plate for assessment purposes.
The test item was investigated in an independent repeat using the preincubation modification in doses of up to and including 500 µg per plate without and with S9 mix. Other experimental conditions remained unchanged. Doses up to and including 16 µg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect. This range could be used strain-specific up to 500 µg per plate for assessment purposes.
Evidence of mutagenic activity of the test item was not seen. No biologically relevant increase in the mutant count, in comparison to the solvent controls, was observed in any of the strains tested, without and with S9 mix, in the plate incorporation as well in the preincubation modification, under the experimental conditions applied. Therefore, the test substance was considered to be non-mutagenic with and without S9 mix in the Salmonella/microsome test (Nern/Bayer AG, 2014).
Ames test by Gahlmann, 1992: The test substance was investigated using the Salmonella/microsome test according to OECD guideline 471 for point mutagenic effects in doses up to 5000 µg per plate on four histidine-auxotrophic Salmonella typhimurium LT2 mutant strains (TA 1535, TA 100, TA 98, and TA 1537).
Doses up to and including 50 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no inhibition of growth was observed. At higher doses, the substance had a strong bacteriotoxic effect, but this range could nevertheless be used for assessment purposes.
The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2 -phenylene diamine and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.
Evidence of mutagenic activity of the test substance was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. Therefore, the test substance was considered to be non-mutagenic with and without S9 mix in the Salmonella/microsome test (Gahlmann/Bayer AG, 1992).
The study was performed to investigate the potential of Dichlortoluol-Gemisch to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The highest concentration in the pre-experiment (1640.0 µg/mL) was equal to a molar concentration of about 10 mM, with respect to the purity of the test item (98.4 %). The dose range of the main experiments was limited by test item induced cytotoxicity.
No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments. Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.
In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, Dichlortoluol-Gemisch is considered to be non-mutagenic in this HPRT assay (Hall/ Lanxess, 2010).
In vivo:
A micronucleus test according to OECD guideline 474 was employed to investigate the test substance dichlorotoluene (mixture of isomers) in male and female mice for a possible clastogenic effect on the chromosomes of bone marrow erythroblasts. The known clastogen and cytostatic agent, cyclophosphamide, served as control.
The treated animals received a single intraperitoneal administration of either the test substance or cyclophosphamide. The femoral marrow of groups treated with the test substance was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of the test substance and the positive control, cyclphosphamide, were 1500 and 20 mg/kg body weight, respectively.
The animals treated with the test substance showed symptoms of toxicity (apathy, stretching of body, roughed fur, staggering gait, spasm and difficulty in breathing) after administration. However, all animals survived until the end of the test.
There was no altered ratio between polychromatic and normochromatic erythrocytes.
Cyclophosphamide, the positive control, had a clear clastogenic effect, as is shown by the biologically relevant increase in polychromatic erythrocytes with micronuclei. The ratio of polychromatic to normochromatic erythrocytes was not altered.
No indications of a clastogenic effect of the test substance dichlorotoluene (mixture of isomers) were found after a single intraperitoneal treatment with 1500 mg/kg (Herbold/ Bayer AG, 1993).
Short description of key information:
In vitro:
Two Ames tests are available: In one test 5 strains were tested, in the
other 4 strains were used.
Additionally, the test item was tested in an HPRT assay according OECD
Guideline study 476. Under the experimental conditions reported the test
item did not induce gene mutations at the HPRT locus in V79 cells and
therefore was considered to be non-mutagenic in this HPRT assay (Hall/
Harlan/ Lanxess, 2010).
In vivo:
In a micronucleus test according to OECD guideline 474 no indications of
a clastogenic effect of the test substance dichlorotoluene (mixture of
isomers) were found after a single intraperitoneal treatment with 1500
mg/kg (Herbold/ Bayer AG, 1993).
Overall, it can be concluded that the compound is not genotoxic in vitro
or in vivo.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
All available in vitro and in vitro tests are negative. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification for genetic toxicity is not justified.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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